OP0031 SHARED AND DISTINCT GUT MICROBIOME SIGNATURES IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS AND ITS RELATED IMMUNE-MEDIATED DISEASES

Background:Immune-mediated diseases such as spondyloarthritis (SpA) consistently coincide with dysbiosis of the gut microbiota and frequently present with additional inflammatory pathologies such as Crohn’s disease (CD) and acute anterior uveitis (AAU). Deep profiling of gut microbiota may reveal new pathways of how SpA and its related diseases are initiated and perpetuated.Objectives:To identify the presence of shared and specific gut microbiota signatures for SpA and its related diseases as a whole, as well as for the individual diseases, relative to healthy controls.Methods:Patients were recruited with a definite diagnosis of axial SpA, AAU or CD and were compared to controls (patients with back pain and previously ruled out SpA/CD/AAU diagnosis). All patients were naïve to or did not receive treatment with biological disease-modifying antirheumatic drugs for at least 3 months before enrollment of the study. Fecal samples were collected and microbiota composition was determined by 16S rRNA gene sequencing, followed by computational analysis referencing the SILVA138 database. Nonparametric Wilcoxon tests were used to calculate differential abundances between binary groups, and the Spearman correlation was used with continuous covariates. Nested linear models and likelihood ratio tests were used to assess confounding with respect to patient characteristics, HLA-B27 expression, inflammatory markers, and the presence of other immune-mediated diseases.Results:A total of 300 patients were recruited for the study: 111 axial SpA, 110 AAU, and 79 CD patients and were compared to 63 control individuals. Fifty-three of patients were males with an age (mean±SD) of 39.1±12.3 years. The prevalence of HLA-B27 was 63.0% by patients compared to 7.9% by control individuals. A multivariate PERMANOVA test between the groups was significant (p<0.001), revealing a difference in overall composition between the groups.At the phylum level, patients with axial SpA, AAU and CD contained higher abundances of Proteobacteria, Bacteroidetes and Fusobacteria, and lower abundances of Firmicutes and Actinobacteria compared to the control group. At the genus level, patients (with axial SpA, AAU and CD) displayed a shared gut microbiome signature differing from that of control individuals. Patients samples were strongly depleted in Blautia compared to the control group. Many of the differentially abundant taxa also correlated with increased inflammation as measured by C-reactive protein (CRP), including a depletion of Fusicatenibacter, Lachnospiraceae FCS020 and Roseburia, as well as an enrichment of Lactobacillus and Veillonella. By looking at each separate disease phenotype, CD patients differed significantly from the control individuals with respect to many genera. These primarily consisted of depletions in Clostridiales (Roseburia, Coprococcus, Ruminococcaceae), and enrichments of pathogen-harboring genera such as Escherichia-Shigella and Fusobacterium. Axial SpA patients were uniquely enriched in Collinsella and Holdemanella and depleted in Cupriavidus; the enrichment of Lactobacillus and depletion of Blautia observed in all patient groups was also associated to the presence of axial SpA, though confounded by CRP. There were strong taxa associations to the presence of HLA-B27, including enrichment of Asteroleplasma, Coprococcus, Faecalibacterium, Rominococcaceae, Lachnospiraceae NK4A136 and Rikenellaceae.Conclusion:There is a robust shared taxonomic signature among related immune-mediated diseases, in addition to individual disease phenotype signatures. Patients frequently exhibited a strong depletion in Blautia and an enrichment in Lactobacillus as well as pathogen-harboring genera such as Escherichia-Shigella and Fusobacterium.Figure 1.Taxa associations within and between the groups resulting from comparing each with the control group and accounting for disease concomitance and patient characteristics (FDR ≤ 0.05). AAU, anterior acute uveitis; CD, Crohn’s disease; SpA, spondyloarthritis.Disclosure of Interests:None declared

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Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome

Scientific Reports ◽

10.1038/s41598-021-97083-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yue Hu ◽

Fang Chen ◽

Haiyong Ye ◽

Bin Lu

Keyword(s):

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Rat Model ◽

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Metabolic Phenotype ◽

Control Group ◽

Rrna Gene ◽

Microbial Dysbiosis ◽

Irritable Bowel

AbstractStress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.

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Decreased Enteric Bacterial Composition and Diversity in South American Crohn’s Disease Vary With the Choice of Treatment Strategy and Time Since Diagnosis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz189 ◽

2019 ◽

Vol 14 (6) ◽

pp. 791-800

Author(s):

Angélica Cruz-Lebrón ◽

Leticia D’argenio Garcia ◽

Aarthi Talla ◽

Samira Joussef-Piña ◽

Miguel E Quiñones-Mateu ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Bacterial Diversity ◽

Relative Abundance ◽

Treatment Strategy ◽

Chronic Inflammatory Disease ◽

Rrna Gene ◽

Faecal Calprotectin ◽

Time Since Diagnosis

Abstract Background and Aims The symptomology of Crohn’s disease [CD], a chronic inflammatory disease of the digestive tract, correlates poorly with clinical, endoscopic or immunological assessments of disease severity. The prevalence of CD in South America is rising, reflecting changes in socio-economic stability. Many treatment options are available to CD patients, including biological agents and corticosteroids, each of which offers variable efficacy attributed to host genetics and environmental factors associated with alterations in the gut microbiota. Methods Based on 16S rRNA gene sequencing and taxonomic differences, we compared the faecal microbial population of Brazilian patients with CD treated with corticosteroid or anti-tumour necrosis factor [anti-TNF] immunotherapy. Faecal calprotectin and plasma sCD14 levels were quantified as markers for local and systemic inflammation, respectively. Results Anti-TNF treatment led to an increased relative abundance of Proteobacteria and a decreased level of Bacteroidetes. In contrast, corticoid treatment was associated with an increase in the relative abundance of Actinobacteria, which has been linked to inflammation in CD. Disruption of the faecal microbiota was related to decreased bacterial diversity and composition. Moreover, the choice of clinical regimen and time since diagnosis modulate the character of the resulting dysbiosis. Conclusions Enteric microbial populations in CD patients who have been treated are modulated by disease pathogenesis, local inflammatory microenvironment and treatment strategy. The dysbiosis that remains after anti-TNF treatment due to decreased bacterial diversity and composition abates restoration of the microbiota to a healthy state, suggesting that the identification and development of new clinical treatments for CD must include their capacity to normalize the gut microbiota.

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Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease

Frontiers in Medicine ◽

10.3389/fmed.2020.606298 ◽

2020 ◽

Vol 7 ◽

Author(s):

Jagadesan Sankarasubramanian ◽

Rizwan Ahmad ◽

Nagavardhini Avuthu ◽

Amar B. Singh ◽

Chittibabu Guda

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Gut Microbiome ◽

Metabolic Pathways ◽

Meta Analysis ◽

Metabolic Effects ◽

Taxonomic Rank ◽

Disease Specific

Background: Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood.Methods: To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. In-silico profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways.Results: Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways.Conclusions: In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.

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Arthritis Associated with Crohn's Disease

Canadian Journal of Gastroenterology ◽

10.1155/1990/517582 ◽

1990 ◽

Vol 4 (8) ◽

pp. 497-502 ◽

Cited By ~ 1

Author(s):

JM Gilvarry ◽

F Keeling ◽

O Fitzgerald ◽

JF Fielding

Keyword(s):

Crohn’S Disease ◽

Ankylosing Spondylitis ◽

Crohn's Disease ◽

Disease Activity ◽

Disease Onset ◽

Close Correlation ◽

Control Group ◽

Hypertrophic Osteoarthropathy ◽

Hla B27 ◽

Peripheral Arthritis

A controlled prospective study was undertaken to determine the incidence and characteristic features of peripheral arthritis, sacroiliitis, ankylosing spondylitis and hypertrophic osteoarthropathy in a group of patients with Crohn's disease, and to define the relationship of such arthritides with disease site, duration and activity. Peripheral arthritis occurred in 14.5% of the patients; it was not seen in the control group. This arthritis, which tended to be pauciarticular, was more common in females with large bowel disease and post dated the bowel symptoms in all but one patient. There was close correlation with disease activity. Radiographic sacroiliitis occurred in 12.7% of the patients and ankylosing spondylitis in 7.3%; neither of these were seen in the control group. Sacroiliitis was more common in females and showed no correlation with either disease activity or human lymphocyte antigen (HLA) B27. Ankylosing spondylitis was seen equally in males and females and showed close correlation with both disease activity and HLA B27. Hypertrophic osteoarthropathy occurred in 9.1% of patients. It was not seen in the control group. All patients were asymptomatic. It showed no correlation with disease activity, finger clubbing, age of disease onset, or HLA B27.

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Treatment with a Monoclonal Anti-IL-12p40 Antibody Induces Substantial Gut Microbiota Changes in an Experimental Colitis Model

Gastroenterology Research and Practice ◽

10.1155/2016/4953120 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

Josué Castro-Mejía ◽

Maja Jakesevic ◽

Łukasz Krych ◽

Dennis S. Nielsen ◽

Lars H. Hansen ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

High Throughput Sequencing ◽

Experimental Colitis ◽

Rrna Gene ◽

Colonic Inflammation ◽

Inflammatory Bowel ◽

And Biological Markers ◽

Colitis Model

Background and Aim. Crohn’s disease is associated with gut microbiota (GM) dysbiosis. Treatment with the anti-IL-12p40 monoclonal antibody (12p40-mAb) has therapeutic effect in Crohn’s disease patients. This study addresses whether a 12p40-mAb treatment influences gut microbiota (GM) composition in mice with adoptive transfer colitis (AdTr-colitis).Methods. AdTr-colitis mice were treated with 12p40-mAb or rat-IgG2a or NaCl from days 21 to 47. Disease was monitored by changes in body weight, stool, endoscopic and histopathology scores, immunohistochemistry, and colonic cytokine/chemokine profiles. GM was characterized through DGGE and 16S rRNA gene-amplicon high-throughput sequencing.Results. Following 12p40-mAb treatment, most clinical and pathological parameters associated with colitis were either reduced or absent. GM was shifted towards a higher Firmicutes-to-Bacteroidetes ratio compared to rat-IgG2a treated mice. Significant correlations between 17 bacterial genera and biological markers were found. The relative abundances of the RF32 order (Alphaproteobacteria) andAkkermansia muciniphilawere positively correlated with damaged histopathology and colonic inflammation.Conclusions. Shifts in GM distribution were observed with clinical response to 12p40-mAb treatment, whereas specific GM members correlated with colitis symptoms. Our study implicates that specific changes in GM may be connected with positive clinical outcomes and suggests preventing or correcting GM dysbiosis as a treatment goal in inflammatory bowel disease.

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The effect of toxic pyridine-alkaloid secondary metabolites on the sunbird gut microbiome

npj Biofilms and Microbiomes ◽

10.1038/s41522-020-00161-9 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Mohanraj Gunasekaran ◽

Maya Lalzar ◽

Yehonatan Sharaby ◽

Ido Izhaki ◽

Malka Halpern

Keyword(s):

Secondary Metabolites ◽

Gut Microbiota ◽

Gut Microbiome ◽

Amplicon Sequencing ◽

Control Group ◽

Rrna Gene ◽

Microbiota Composition ◽

Degrading Bacteria ◽

And Control ◽

Gut Microbiota Composition

AbstractSunbirds feed on tobacco tree nectar which contains toxic nicotine and anabasine secondary metabolites. Our aim was to understand the effect of nicotine and anabasine on the gut microbiota composition of sunbirds. Sixteen captive sunbirds were randomly assigned to two diets: artificial nectar either with (treatment) or without (control) added nicotine and anabasine. Excreta were collected at 0, 2, 4 and 7 weeks of treatment and samples were processed for bacterial culture and high-throughput amplicon sequencing of the 16S rRNA gene. The gut microbiome diversity of the treated and control birds changed differently along the seven-week experiment. While the diversity decreased in the control group along the first three samplings (0, 2 and 4 weeks), it increased in the treatment group. The microbiota composition analyses demonstrated that a diet with nicotine and anabasine, significantly changed the birds’ gut microbiota composition compared to the control birds. The abundance of nicotine- and anabasine- degrading bacteria in the excreta of the treated birds, was significantly higher after four and seven weeks compared to the control group. Furthermore, analysis of culturable isolates, including Lactococcus, showed that sunbirds’ gut-associated bacteria were capable of degrading nicotine and anabasine, consistent with their hypothesised role as detoxifying and nutritional symbionts.

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Influence of Enteral Nutrition on Gut Microbiota Composition in Patients with Crohn’s Disease: A Systematic Review

Nutrients ◽

10.3390/nu12092551 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2551 ◽

Cited By ~ 1

Author(s):

Paulina Horwat ◽

Stanisław Kopeć ◽

Aleksandra Garczyk ◽

Iwona Kaliciak ◽

Zuzanna Staręga ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Enteral Nutrition ◽

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Exclusive Enteral Nutrition ◽

Faecal Samples ◽

Hs Crp ◽

Rrna Gene Sequencing

The aim of the study was to systematically and comprehensively evaluate whether exclusive enteral nutrition (EEN) has impact on gut microbiota in patients with Crohn’s disease (CD). The databases PUBMED (MEDLINE), SCOPUS and WEB OF SCIENCE were searched. Out of 232 studies, 9 met inclusion criteria. The combined analyzed population consists of 118 patients with CD and treated with EEN with a time of intervention of 2–12 weeks. Studies were conducted in children, with the exception of one study. All applied feeding formulas had similar energy value and composition. The microbiome analysis was based on 16S rRNA gene sequencing of faecal samples. In all studies, EEN treatment decreases inflammatory markers (i.e., hs-CRP and FCP). A change in abundance of numerous bacterial families (Clostridiaceae, Eubacteriaceae, Bacteroidaceae) was noticed, especially in Bacteroidaceae. An increase in families connected to the more severe clinical course (Fusobacteria, Prevotella, Lachnospiraceae) was observed in only 2.5% of CD patients. Our analyses suggest EEN has a beneficial influence on gut microbiome in patients with CD, which is interrelated with clinical patient’s improvement and time of disease remission.

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Evidence of Disturbed Gut Microbial Metabolic Activity in Pediatric Crohn’s Disease

Crohn's & Colitis 360 ◽

10.1093/crocol/otz010 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Tommy Sundqvist ◽

Lars Stenhammar ◽

Bo Tjellström ◽

Karl-Eric Magnusson ◽

Tore Midtvedt ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Observational Study ◽

Gut Microbiota ◽

Metabolic Activity ◽

Control Group ◽

Clinical Implications ◽

Healthy Controls ◽

Tryptic Activity ◽

Microbial Metabolic Activity

Abstract Background Dysbiosis, that is, disturbed gut microbial balance, is well documented in Crohn’s disease (CD). We aimed at studying CD-linked dysbiosis in children by analyzing fecal microbe-associated characteristics, previously not reported in children. Methods This observational study included 28 children with active CD and healthy controls. We assessed the following three indicators of gut microbiota metabolism in the feces: the presence of tryptic activity, the conversion of cholesterol to coprostanol, and the conversion of bilirubin to urobilinogen. Results The fecal tryptic activity was significantly higher in children with active CD compared to the control group (P < 0.01). The fecal coprostanol of the CD children was close to zero and differed significantly from the controls (P < 0.001). Furthermore, the children with CD had very low fecal urobilinogen, differing significantly from the control group (P < 0.001). Conclusions The significant differences in levels of fecal bacterial metabolites in patients with active CD compared to healthy controls reflect major perturbation of gut microbial functions and have not previously been reported in children. This fits well with the prevailing concept of a dysbiotic gut microbiota in CD and may have important clinical implications by bringing the dysbiosis back into balance.

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Evaluation of Changes in Gut Microbiota in Patients with Crohn’s Disease after Anti-Tnfα Treatment: Prospective Multicenter Observational Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17145120 ◽

2020 ◽

Vol 17 (14) ◽

pp. 5120

Author(s):

Laura Sanchis-Artero ◽

Juan Francisco Martínez-Blanch ◽

Sergio Manresa-Vera ◽

Ernesto Cortés-Castell ◽

Josefa Rodriguez-Morales ◽

...

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Observational Study ◽

Gut Microbiota ◽

Quantitative Relationship ◽

Control Group ◽

Multicenter Observational Study ◽

Faecalibacterium Prausnitzii ◽

Prospective Multicenter Observational Study

Background: Crohn’s disease is believed to result from the interaction between genetic susceptibility, environmental factors and gut microbiota, leading to an aberrant immune response. The objectives of this study are to evaluate the qualitative and quantitative changes in the microbiota of patients with Crohn’s disease after six months of anti-tumor-necrosis factor (anti-TNFα) (infliximab or adalimumab) treatment and to determine whether these changes lead to the recovery of normal microbiota when compared to a control group of healthy subjects. In addition, we will evaluate the potential role of the Faecalibacterium prausnitzii/Escherichia coli and Faecalibacterium prausnitzii/Clostridium coccoides ratios as indicators of therapeutic response to anti-TNFα drugs. Methods/Design: This prospective multicenter observational study will comprise a total of 88 subjects: 44 patients with Crohn’s disease scheduled to start anti-TNFα treatment as described in the drug specifications to control the disease and 44 healthy individuals who share the same lifestyle and eating habits. The presence of inflammatory activity will be determined by the Harvey-Bradshaw index, analytical parameters in blood, including C-reactive protein, and fecal calprotectin levels at commencement of the study, at three months and at six months, allowing the classification of patients into responders and non-responders. Microbiota composition and the quantitative relationship between Faecalibacterium prausnitzii and Escherichia coli and between Faecalibacterium prausnitzii and Clostridium coccoides group as indicators of dysbiosis will be studied at inclusion and six months after initiation of treatment using ultra sequencing with Illumina technology and comparative bioinformatics analysis for the former relationship, and digital droplet PCR using stool samples for the latter. Upon inclusion, patients will complete a survey of dietary intake for the three days prior to stool collection, which will be repeated six months later in a second collection to minimize dietary bias. Discussion: In this study, massive sequencing, a reliable new tool, will be applied to identify early biomarkers of response to anti-TNF treatment in patients with Crohn’s disease to improve clinical management of these patients, reduce morbidity rates and improve efficiency.

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Alterations of Gut Microbiota in Patients With Intestinal Tuberculosis That Different From Crohn’s Disease

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.673691 ◽

2021 ◽

Vol 9 ◽

Author(s):

Cong He ◽

Huan Wang ◽

Chen Yu ◽

Chao Peng ◽

Xu Shu ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Gut Microbiota ◽

Intestinal Tuberculosis ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Short Chain Fatty Acids ◽

Bacterial Invasion ◽

Rrna Gene ◽

Microbial Structure

Intestinal tuberculosis (ITB) and Crohn’s disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.

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